title: Design and synthesis of stereochemically defined novel spirocyclic P2-ligands for HIV-1 protease inhibitors.
abstract: The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu 3SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported.
authors.affiliation: Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA. akghosh@purdue.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Chapsal
authors.forename: Abigail
authors.initials: A
authors.lastname: Baldridge
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ide
authors.forename: Yashiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
mesh_terms: D015195:Drug Design; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008024:Ligands; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D013141:Spiro Compounds; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1